We have studied the influence of allopurinol, a xanthine oxidase inhibitor, on the systemic levels of 6MP following oral and I.V. administration of a single dose (8 mg/kg) of 6MP. The peak 6MP levels following an oral dose increased from a mean of 4.8 x 10 to the minus seven M without allopurinol to 2.0 x 10 to the minus six M after allopurinol treatment. There was a corresponding 4-fold increase in the area under the curve (AUC) of plasma 6MP concentration vs. time curve. In contrast, pretreatment with allopurinol had no significant effect on the AUC when dose of 6MP was administered I.V. The results suggest that in a clinical setting, oral dose of 6MP may have to be reduced when given in conjunction with allopurinol.